Selenium substitution endows cystine with radiosensitization activity against cervical cancer cells

Xie, Qiang; He, Lizhen; Lai, Haoqiang; Zheng, Wenjie; Chen, Tianfeng

doi:10.1039/c4ra07031c

Cited by 18 publications

(9 citation statements)

References 50 publications

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“…A previous study demonstrated that the anticancer activity of selenium compounds occurred via oxidation of reduced glutathione and other thiols, which also revealed apoptogenic effects and alterations in cell cycle progression mediated by ROS [ 53 ]. Furthermore, Xie and collaborators [ 54 ] showed that a selenium compound could be a strategy for design and further development into effective and low toxicity cancer radiosensitizers, as selenium substitution significantly enhanced X-ray-induced ROS overproduction in cancer cells.…”

Section: Resultsmentioning

confidence: 99%

IP-Se-06, a Selenylated Imidazo[1,2-a]pyridine, Modulates Intracellular Redox State and Causes Akt/mTOR/HIF-1α and MAPK Signaling Inhibition, Promoting Antiproliferative Effect and Apoptosis in Glioblastoma Cells

Santos

Rafique

Saba

et al. 2022

Oxidative Medicine and Cellular Longevity

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Glioblastoma multiforme (GBM) is a notably lethal brain tumor associated with high proliferation rate and therapeutic resistance, while currently effective treatment options are still lacking. Imidazo[1,2-a]pyridine derivatives and organoselenium compounds are largely used in medicinal chemistry and drug development. This study is aimed at further investigating the antitumor mechanism of IP-Se-06 (3-((2-methoxyphenyl)selanyl)-7-methyl-2-phenylimidazol[1,2-a]pyridine), a selenylated imidazo[1,2-a]pyridine derivative in glioblastoma cells. IP-Se-06 exhibited high cytotoxicity against A172 cells ( I C 50 = 1.8 μ M ) and selectivity for this glioblastoma cell. The IP-Se-06 compound has pharmacological properties verified in its ADMET profile, especially related to blood-brain barrier (BBB) permeability. At low concentration (1 μM), IP-Se-06 induced intracellular redox state modulation with depletion of TrxR and GSH levels as well as inhibition of NRF2 protein. IP-Se-06 also decreased mitochondrial membrane potential, induced cytochrome c release, and chromatin condensation. Furthermore, IP-Se-06 induced apoptosis by decreasing levels of Bcl-xL while increasing levels of γ-H2AX and p53 proteins. Treatment with IP-Se-06 induced cell cycle arrest and showed antiproliferative effect by inhibition of Akt/mTOR/HIF-1α and ERK 1/2 signaling pathways. In addition, IP-Se-06 displayed significant inhibition of p38 MAPK and p-p38, leading to inhibition of inflammasome complex proteins (NLRP3 and caspase-1) in glioblastoma cells. These collective findings demonstrated that IP-Se-06 is a bioactive molecule that can be considered a candidate for the development of a novel drug for glioblastoma treatment.

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Section: Resultsmentioning

confidence: 99%

IP-Se-06, a Selenylated Imidazo[1,2-a]pyridine, Modulates Intracellular Redox State and Causes Akt/mTOR/HIF-1α and MAPK Signaling Inhibition, Promoting Antiproliferative Effect and Apoptosis in Glioblastoma Cells

Santos

Rafique

Saba

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…In the past decades, a great number of studies demonstrated that Se species are promising agents for cancer therapeutics, due to their capability of generating reactive oxygen species (ROS), which can induce apoptosis in tumor cells . Interestingly, Se‐containing compounds combined with radiotherapy appeared to specifically enhance the radiosensitivity of cancer cells resulting in a wave of selenium related publications . It needs to be mentioned that the mechanism of action of selenium is still not well‐understood.…”

Section: Enhancing the Effect Of Ionizing Radiationmentioning

confidence: 99%

“…[88,89] Interestingly, Secontaining compounds combined with radiotherapy appeared to specifically enhance the radiosensitivity of cancer cells resulting in a wave of selenium related publications. [90][91][92] It needs to be mentioned that the mechanism of action of selenium is still not well-understood. An increase in ROS levels was observed when combining Se compounds with radiotherapy, which is not necessarily only related to the production of secondary electrons, but may have a different origin.…”

Section: Selenium Nanocarriersmentioning

confidence: 99%

Enhanced Cancer Therapy by Combining Radiation and Chemical Effects Mediated by Nanocarriers

Denkova

Liu

Men

et al. 2020

Advanced Therapeutics

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Next to surgery, radiotherapy and chemotherapy are the two most commonly applied treatments against cancer. These therapies are often combined, but the therapeutic outcome is still limited. Nanocarriers may be the solution to many of the issues encountered when combining these therapies. In this review, the role of nanocarriers in combined radiotherapy and chemical cancer treatment is discussed, divided into four distinct strategy classes. For each strategy, examples of the literature are given to come eventually to conclusion on the possible translation to the clinic.

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“…(Tiekink, 2012). Selenium can act as an effective radiosensitizer to enhance the anticancer efficacy through induction of cancer cell apoptosis (Xie, He, Lai, Zheng, & Chen, 2014). Motivated by the potential utility of selenium and tellurium against a number of diseases and pathological conditions, we have undertaken this study in order to fill the gap in structural characteristics of the two substituted tri-peptides.…”

Section: Figure 1 Schematic Representation Of Gshmentioning

confidence: 99%

Structural Modeling of Glutathiones Containing Selenium and Tellurium

Nascimento¹,

Melnikov²,

Lanoa³

et al. 2016

IJC

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The comparative structural modeling of reduced and oxidized glutathiones, as well as their derivatives containing selenium and tellurium in chalcogen sites (Ch = Se, Te) has provided detailed information about the bond lengths and bond angles, filling the gap in the structural characteristics of these tri-peptides. The investigation using the molecular mechanics technique with good approximation confirmed the available information on X-ray refinements for the related compounds. It was shown that Ch-H and Ch-C bond lengths grow in parallel with the increasing chalcogen ionic radii. Although the distances C-C, C-O, and C-N are very similar, the geometry of GChChG glutathiones is rich in conformers owing to the possibility of rotation about the bridge Ch-Ch. It is confirmed that the distances Ch-Ch are essentially independent of substituents in most of chalcogen compounds from elemental chalcogens to oxydized glutathiones. The standard program Hyperchem 7.5 has proved to be an appropriate tool for the structural description of less-common bioactive compositions when direct X-ray data are missing.

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Selenium substitution endows cystine with radiosensitization activity against cervical cancer cells

Abstract: Selenium substitution could endow cystine the radiosensitization activity against cervical cancer HeLa cells through overproduction of ROS and activation of downstream signaling, which suggests this could be a novel strategy for design of cancer radiosensitizers.

Cited by 18 publications

References 50 publications

IP-Se-06, a Selenylated Imidazo[1,2-a]pyridine, Modulates Intracellular Redox State and Causes Akt/mTOR/HIF-1α and MAPK Signaling Inhibition, Promoting Antiproliferative Effect and Apoptosis in Glioblastoma Cells

IP-Se-06, a Selenylated Imidazo[1,2-a]pyridine, Modulates Intracellular Redox State and Causes Akt/mTOR/HIF-1α and MAPK Signaling Inhibition, Promoting Antiproliferative Effect and Apoptosis in Glioblastoma Cells

Enhanced Cancer Therapy by Combining Radiation and Chemical Effects Mediated by Nanocarriers

Structural Modeling of Glutathiones Containing Selenium and Tellurium

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